Involvement of the Bcl2 gene family in the signaling and control of retinal ganglion cell death.
Retinal ganglion cell death by apoptosis is a well-established outcome in the glaucomatous pathology of the retina. Extensive research into the molecular events underlying this process show us that members of the Bcl2 gene family play a critical role in the activation and control of ganglion cell death. Perhaps the most critical molecule at play is the pro-apoptotic protein BAX. Without BAX, ganglion cell somas appear to survive an optic nerve insult indefinitely. Once BAX is activated, however, the cell death program reaches an irreversible point, where the process cannot be blocked. Interacting with BAX are other members of this larger gene family, including the anti-apoptotic protein BCL-X, and several members of the BH3-only proteins that serve as sensors and activators of the cell death program. A hypothetical model of how all these molecules interact in glaucoma is presented.
Nickells
Robert W
RW
Department of Ophthalmology and Visual Sciences University of Wisconsin, Madison, WI 53706, USA. nickells@wisc.edu
Semaan
Sheila J
SJ
Schlamp
Cassandra L
CL
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019254:Genes, bcl-2; D005901:Glaucoma / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein